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Kidney Week

Abstract: FR-PO057

A New Mouse Model for Septic AKI with Vasopressor Support

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Halasa, Brianna C., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Street, Jonathan, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Yuen, Peter S.T., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Star, Robert A., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
Background

Sepsis, a common cause of acute kidney injury (AKI), is a dysregulated host response to infection that leads to multiple organ dysfunction. Currently, there is no specific therapy for sepsis/AKI. Patients with sepsis-induced AKI are treated with supportive care including fluids and vasopressors to manage hypotension. While blood pressure maintenance in sepsis patients is routine, blood pressure measurement and management is notoriously absent in small animal models. We established a mouse model of septic-AKI with conscious hemodynamic monitoring and vasopressor treatment. We hypothesize that stabilizing blood pressure with norepinephrine (NE) will partially mitigate the severity of sepsis-AKI, perhaps changing the responsiveness to specific treatments.

Methods

In CD-1 mice (n=22), we inserted a telemetry device into the left carotid artery to monitor blood pressure, and catheterized the right jugular vein for IV drug delivery. After recovery, sepsis-AKI was induced by cecal ligation and puncture (CLP). NE was administered IV via an osmotic minipump. Hemodynamics were recorded by telemetry from 24 hr before to 24 hr post-CLP. Glomerular filtration rate (GFR) was measured by loss of transcutaneous fluorescence of IV injected FITC-sinistrin.

Results

Surgical anesthesia caused transient 1 hr hypotension and bradycardia. Despite variability, septic NE-treated mice fell into 2 groups. In the first group (n=8), the effect of NE was short. The blood pressure increased for ~4 hr then dropped to septic-shock levels (<65mmHg). In the second group (n=12), NE effect lasted longer. The blood pressure rose to normal (90-110 mmHg) and remained constant for ~20 hr. In 2 outliers, the blood pressure fluctuated over 24 hr. The heart rate was consistent in all groups; returning to normal (650-750 bpm), then decreasing 3-5 hr later. We measured GFR in mice that survived to 24 hr; 2 mice from the second group had a normal GFR of 742 and 871 uL/min/100gBW.

Conclusion

We successfully delivered intravenous NE and monitored hemodynamics in septic mice. We found substantial mouse to mouse variability in blood pressure, making it crucial to monitor individual NE responses. NE had the expected hemodynamic response in blood pressure stability in over half of the mice.

Funding

  • NIDDK Support